Fuchs' Heterochromic Uveitis: a Reappraisal of the Clinical Spectrum

Eye (1991) S, 64 9-661

Fuchs' Heterochromic Uveitis: A Reappraisal of the Clinical Spectrum

NICHOLAS P. JONES Manchester

Summary The varying clinical appearance within a group of 103 patients with Fuchs' Hetero chromic Uveitis (FHU) is discussed. Bilateral cases accounted for 7.8% of patients. Cataract was found in 80.2% of cases after 8.8 years mean follow-up, and glaucoma affected 26.2% of patients. The most important diagnostic criteria are the typical pattern of iris atrophy and depigmentation, the characteristic intraocular inflam mation, and complicated cataract. These are described in detail. The correct diag nosis of FHU is important because it affects future management and prognosis. The presence or absence of macroscopic heterochromia is not a helpful component of the ocular examination and should play little part in diagnosis. FHU does not necessarily present in its classical form, and may first resemble acute anterior uveitis or pars planitis. The syndrome may be the end stage of a number of different conditions.

Although the combination of heterochromia tis (FHU) has placed into perspective some of and cataract was noted in 1843 by Lawrence, I the accepted criteria for diagnosis, has and later by others2,3 it was not until 1906 that allowed further comment on some aspects of Ernst Fuchs comprehensively described a previous reports, and has brought to light group of 38 patients with signs of a form of some features not previously discussed in heterochromia with inflammation and catar detaiL The clinical spectrum of FHU is wider act, dubbed 'complicated heterochromia',4 than has been previously defined, and the The syndrome which now bears his name has clinical course is more variable, Studies on a interested many authors in the succeeding 85 cohort of 103 patients with FHU are reported. years and some series of considerable size have been published,5-8, The classical diag nostic criteria for the condition were reiter Patients and Methods ated in 1955 by Franceschetti5 and include the Commencing in 1987, all new and old patients presence of stellate keratic precipitates, a seen at the Manchester Royal Eye Hospital characteristic pattern of iris atrophy, with or with a definiteor suggested diagnosis of FHU, without nodules (and without posterior syn were referred to and examined by the author, echiae), vitreous opacification, cataract and In all cases a detailed history was taken, possibly glaucoma, A comprehensive review9,10 including mode of, and reason for, presen of the literature was published in 1973. tation, General medical, neonatal, gesta The critical examination of a large number tional and family histories were included. The of patients with Fuchs' Heterochromic Uvei- clinical course of the disease process was

Correspondence to: Mr. N. P. Jones, FRCS, FCOphth, University Department of Ophthalmology, Manchester Royal Eye Hospital, Oxford Road, Manchester M13 9WH. 650 N. P. JONES noted, including a record of medical and sur distinct groups; fifteen patientshad congeni gical management. tal heterochromia and 25 had noticed a later A full clinical examination included onset. The age at which the heterochromia appraisal of facial appearance, slit-lamp bio was firstnoticed, for the 25 patients in which it microscopy including a critical examination of was not congenital, is shown in Fig. 2). cornea, anterior chamber and iris, applana A previous ophthalmic history revealed tion, and dilatation for fundoscopy. Corneal that 16 patients (15.5%) had had poor vision endothelial specular microscopy and haemat in the affected eye since childhood, but none ological investigations were performed in had presented to an ophthalmologist at that selected cases. Most patients have been exam stage. A lower best visual acuity on the ined on several occasions by the author. A affectedside (in those with clear media and no total of 128 patients were referred with a defi macular disease) implied amblyopia. There nite or suggested diagnosis of FHU. Of these, was no history of strabismus in any of these 103 were considered to fulfil criteria for this patients. Only three patients had significant diagnosis and were included in the survey. anisometropia, the affected eye being more myopic in all three cases. No patient had evi Results dence of amblyopia in the eye without inflam The patients' ages at presentation are shown mation. Of these patients with amblyopia, graphically in Fig. 1. The range was 8 to 71 nine were aware of their heterochromia, and years, with a mean of 36. 1 years. The major in four cases it was definitelyacquired, at ages symptoms at presentation are shown in 17, 21, 35 and 38 years, respectively. Two Table 1. The follow-up since presentation has patients remembered a blunt anjury of some a range of six months to 59 years, with a mean significance to the involved eye at some time of 8.8 years. Fifty patients (48.5%) were male previously. Nineteen patients complained of and 53 (51.5%) female. Ninety-five patients eye or brow ache before or since presentation. (92.2%) were Caucasian, three Asian and five Three patients were aware of a significant Afro-caribbean or mixed race (total 7.8% maternal illness during pregnancy. One non-Caucasian). The precise catchment mother had serum hepatitis, one had epileptic population of this hospital cannot be defined, fits (the reason being unknown), and another but the racial balance of these patients prob required transfusion. Ninety-eight patients ably does not indicate any racial predilection were delivered vaginally at term without inci for the disease. dent. Five patients were delivered with The diagnosis of FHU was not always made forceps, of whom one was known to have sus immediately on presentation. The delay in tained an ocular injury, and one claimed to diagnosis ranged from 0 to 57 years, with a have been injured. The only significant prob mean of 3.4 years. Table II shows the diag lem in the neonatal period involved one noses made on presentation. patient with a ventricular septal defect which The degree of heterochromia was graded required closure. 0-4 by the author. Heterochromia was absent In no patient in this series was evidence (Grade 0) in 10 patients, of whom eight found of a positive familial association for (7.8%) had bilateral disease and two had dark FHU or any other variety of heterochromia. brown irides. Heterochromia Grade 1-4 was On the contrary, discordance in a pair of present in the remaining 93 patients (90.3%) monozygotic twins has been discovered. The but was extremely subtle (Grade 1) in 42 implications of this on any genetic theory for cases, though usually still apparent with the FHU are discussed elsewhere. II naked eye. In a small number of patients, het Enquiries into the general health of these erochromia could only be definedby compari patients revealed the following; three patients son of anterior segment photographs. have peptic ulceration, two systemic hyper Of those patients with heterochromia, 40 tension, and one each have Addison's (43.0% ) were already aware of this fact. All of disease, hypernephroma, diabetes, epilepsy, these patients knew the time of onset of their pernicious anaemia, Parkinsonism, ischaemic heterochromia, and appeared to fall into two heart disease, discoid lupus erythematosus, FUCHS' HETEROCHROMIC UVEITIS: A REAPPRAISAL OF THE CLINICAL SPECTRUM 651

2 NUMBER OF PATIENTS acellular on specular microscopy, and one cor 0 nea showed linear marks in Descemet's mem brane typical of previous trauma and r- 5 consistent with a history of forceps damage

� during delivery.

c- Keratic precipitates (KP) were present in 0 o- 93 eyes (83.8%). The distribution of precip r- � itates was variable, yet seemed to fitinto three r 1 broad patterns (Fig. 3); generalised, affecting the whole posterior cornea (57 eyes); central nn I In II 1-1'1 (16 eyes); and inferior (20 eyes), often dif -5 -10 -15 -20 -25 -30 -35 -40 -45 -50 -55 -60 -65 -70 -75 fusely so but occasionally in a triangular distri AGE AT PRESENTATION bution more commonly associated with acute Fig. 1. The age range of patients with FHU at first presentation to an ophthalmologist. anterior uveitis. The morphology of KP was variable, but many eyes (45, 40.5%) showed previous tuberculosis, and Factor VII defi precipitates previously described as typical of ciency. One patient is a haemophilia carrier. FHU,5.12 that is, stellate with fibrillary exten On examination, the right eye was affected sions, and tiny interspersed fibrils. A dia in 50 cases (48.5%) and the left in 45 (43.6%), grammatic example of a typical area of such the remaining eight patients being bilateral. keratic precipitates is shown in Fig. 4. Nine Head or facial appearance was notable in only teen eyes (17. 1%) had KP which are two cases, both of whom were affected by the described as 'glassy', being medium-sized, Parry-Romberg syndrome of hemifacial atro globular, transparent and non-pigmented. phy on the affected side. Ten patients had a Old pigmented KP were seen in five eyes. partial ptosis on the affected side, of whom There was some correlation between mor eight had undergone cataract surgery. No phology of KP and their distribution. Typi patient in this series had acceptable evidence cally stellate KP were centrally or generally distributed (38 of 45 eyes, 84.4%). Only seven of Homer's syndrome. The cornea of the affec ed eye, examined of 20 eyes (35%) with inferiorly-distributed . � with the slit-lamp biomicroscope, was KP showed stellate characteristics. Anterior chamber activity was recorded abnormal in 17 eyes (15.3%) of whom eight + + +. had previously undergone cataract surgery. traditionally on a scale of 0 to Fifty nine eyes (53. 1 %) had no cellular activity and Three corneas were partially or completely (+). decompensated, two following cataract sur 49 eyes (44. 1 %) had few cells only How ever, two eyes had + + cells and one eye, gery. Eight corneas (7.2%) exhibited a per + + + ipheral, circumferential haze of the deep . Anterior chamber flarewas an uncom stroma and endothelium. Two endothelia had mon finding. Sixteen eyes (14.4%) had typical numerous guttata. Three endothelia signs of FHU including iris atrophy, hetero exhibited a striking abnormality consisting of chromia and cataract, yet had lost any evi multiple scalloped-out patches which were dence of intraocular inflammation (no active Table I Major presenting symptoms in 103 patients Table II The initial diagnosis made in the 103 patients with Fuchs's heterochromic uveitis. (NB some patients eventually diagnosed as Fuchs's heterochromic uveitis have more than one presenting symptom) Number of Number of Diagnosis patients % Symptom patients Fuchs's heterochromic uveitis 65 63 .1 Decreased vision 54 Acute anterior uveitis 20 19 .4 Floaters 34 Pars planitis 8 7.8 Discomfort 12 Phakolytic glaucoma 1 1.0 Heterochromia/uveitis noted by optician No diagnosis made 9 8.7 or other doctor 6 Other 6 Total 103 100.0 652 N. P. JONES

NUMBER OF F¥.TIENTS the entire surface (but always more 10 lfIS numerous in the pupillary area, Fig. 5) and one patient had numerous refractile Russell bodies. Cicatricial posterior synechiae were seen in four patients, all of whom had pre viously had cataract surgery. Although no 5 transient synechiae were seen, in five patients who were phakic, radial stripes of iris epi thelial pigment were seen on the anterior lens surface, indicating previous adhesion (Fig. 6). Iris neovascularisation was an uncommon � � 4 ______finding but was definitely observed in six eyes AGE AT ONSET OF HETEROCHROMIA and is discussed elsewhere.17 Iris haemor Fig: 2. The age at which heterochromia was first rhage following paracentesis or during catar noticed by those patients in whom it was acquired. act surgery has previously been discussed.13.l4 In this survey, filiform haemorrhage following KPs, no cellular activity in anterior chamber applanation tonometry was observed in two or vitreous, no iris nodules). In all 16 cases the eyes on one occasion each. eye had previously undergone cataract The crystalline lens was completely clear in surgery. 22 eyes (19.8%). The remaining 89 eyes had Examination of the iris included a separate a degree of cataract (32 eyes, 28.8%) or had assessment of the degree of atrophy of undergone cataract surgery (57 eyes, 51.3%). anterior border layer, stroma and pigment Of these latter, posterior chamber intraocular epithelium on a scale of 0 (normal) to three lenses (IOLs) were implanted in 27 cases, iris (very severe), and the presence or absence of supported 10Ls in six cases, and the rest nodules, vessels or synechiae was noted. The underwent cataract extraction without IOL findingsin relation to iris atrophy are shown in implantation. The results of modern extra Table III. The vast majority of patients had capsular cataract surgery in FHU have now complete loss of the anterior border layer pig 14-16 been described, including 30 of the above ment. The pattern of pigment epithelial atro 1 57 eyes. 4 The mean duration of disease since phy was extremely variable but a particular diagnosis was 10.4 years for those with catar predilection was noted for the area adjacent act and 6.0 years for those with clear lenses. A to the pupil (affected alone in 16 cases, small number of patients in this series had 14.4%) and the iris periphery (affected alone in 10 cases, 9.0%). The remaining 35 patients with pigment epithelial atrophy showed scat tered transillumination defects. No patient had an atrophic sector. The pigment ruff appeared particularly vulnerable and was patchy or absent in 59 eyes (53.1% ). Iris nodules were a frequent feature in these patients. Fifteen patients had active Koeppe nodules, four had Busacca nodules covering

...... , ...... " : . : . . ) .. . -.: ...... : : - : : . 8··.·: ··(1)··· ·· (1). : ' WIDESPREAD CENTRAL INFERIOR Fig. 4. A drawing of a small area of typical KP 111 Fig. 3. The distribution of KP in this series: Three. FHU, being stellate or dendritic with fine intersperllR" broad categories. fibrils. FUCHS' HETEROCHROMIC UVEITIS: A REAPPRAISAL OF THE CLINICAL SPECTRUM 653

Table III Degree of iris atrophy, on a scale of 0-3, for itating vitrectomy. Of the remaining 47 eyes, each iris layer (number of patients in each category) 15 could not be assessed owing to cataract for mation. The remaining 22 eyes (19.8%) had Degree of completely clear vitreous humour. iris atrophy Examination of the fundus was performed Iris Layer 0 J 2 3 wherever possible, but there was an inade quate view in 10 eyes. Choroidal scars resem Anterior border layer 5 17 16 73 bling old toxoplasmosis were present in eight Stroma 12 47 43 9 eyes (7.2%), as reported in other series,18,l9 Pigment epithelium 50 32 23 6

Discussion stellate precipitates on the back of the crys Some of the above information merely reiter talline lens, always inferiorly, yet none were ates and reinforces previous reports on FHU. seen on the anterior surface. There are however certain features worthy of At some stage in the disease process, 27 separate discussion: patients (26.2%) were treated for glaucoma. The aetiology, management and outcome of A. The History the glaucoma in these patients are reported This survey draws attention to various useful elsewhere. 17 features of the history which may suggest Vitreous opacification of some degree was FHU. In this series visual loss, usually dae to present in 74 eyes (66.6%), consisting of cel cataract formation, was the commonest lular activity, deposition of precipitates on vit reason for presentation, but a complaint of reous architecture (some of these clearly floaters is also frequent and in this age group stellate), and veil formation. Three of these should alert one to the possibility of FHU. patients had complete opacification, necess- Ocular or periocular aching, although pre-

Fig. 5. FHU affecting the right eye with mild heterochromia. Both Koeppe (pupil margin) and Busacca (iris surface) nodules are present. 654 N. P. JONES

Fig. 6. FHU affecting the left eye. Complete absence of anterior border layer pigment, and radial stripes of iris epithelial pigment,deposited on the anJerior lens surface, probably indicating previous sites of adhesion by 'sticky' Koeppe nodules. viously mentioned in connection with FHU,7,8 A traumatic aetiology for FHU has been was found to be common in this series, affect suggested in the past. Several patients in this ing 19 patients (18.4%), but was not associ series reported significant trauma, but the sig ated with an identifiable cause, such as ciliary nificance of this is dubious. One patient had spasm or raised intraocular pressure, in con evidence of forceps injury during parturition. trast to Liesegang's patients.7 No other patient had acceptable evidence of Sixteen eyes with FHU had poor visual intraocular damage from injury. There was acuity of long standing, which could not be inadequate evidence to support the hypoth explained fully by their current disease pro esis that some patients with FHU may have a cess. No patient had evidence of strabismic traumatic aetiology. There was no evidence of amblyopia, and only one patient had gross increased maternal illness in pregnancy or of anisometropia, the axial length of the affected significant acquired illness during infancy or eye being 3.5 mm greater than its fellow. childhood. Fuchs' heterochromic uveitis can commence Two patients in this series have the PaIT)' in childhood. In the absence of another cause Romberg syndrome of hemifacial atrophy, of amblyopia, it is possible that intraocular This condition has previously been linked to inflammation in childhood, with significant FHU 20,21 yet Loewenfeld and Thompsonll , vitreous opacification, may lead to a degree of have disputed the connection. The two stimulus deprivation. This possibility seems patients in this series have mild chronic uveitis unlikely however, and at present the cause of with stellate keratic precipitates, iris atrophy this high occurrence of amblyopia is typical of FHU, and other features of the unknown. It has not previously been men disease. The argumentlO that patients with tioned in reports of FHU and should suggest hemifacial atrophy have heterochromic uvei FHU ratherthan another form of uveitis. tis of a different aetiology to patients with FUCHS' HETEROCHROMIC UVEITIS: A REAPPRAISAL OF THE CLINICAL SPECTRUM 655

Fig. 7. Profound heterochromia due to left-sided FHU. The heterochromia is entirely due to loss of anterior border layer pigment.

Fuchs' syndrome is largely semantic, A single dark brown. It appears to be characteristic of aetiology for all patients with FHU is an FHU that atrophy of the ABL occurs early in assumption which may prove to be incorrect. the course of the disease. The vast majority of The above, reiterated association with the the above patients had severe ABL atrophy Parry-Romberg syndrome may provide one with complete depigmentation (Fig. 7). In example of a different aetiology for FHU, some patients the depigmented ABL is revealed as whitish areas on the stromal sur The Iris B. face (Fig, 8). The normal iris has an immense variability in It is the depigmentation of this layer above structure and pigmentation,z2 yet certain ana all others, which is responsible for hetero tomical features allow the identification of chromia in FHU. changes common to all patients with FHU. It is convenient to consider three separate layers b. The Stroma in this clinical context, Visibility of stromal architecture is dependent on the degree of stromal pigmentation. The a. The Anterior Border Layer denser the pigmentation, the less well defined The anterior border layer (ABL) is seen as an the structure. At one extreme, a light blue anterior stromal condensation, covering a stroma will have an easily visible radial fibril variable proportion of the iris, often fenes lary structure, visible (normal) radial vessels, trated, most dense about the collarette, and of a visible sphincter pupillae, and in some cases extremely variable pigmentation. It is most direct visibility of the pigment epithelium easily visible when dense, and when stromal through absolute stromal defects (crypts). At pigmentation is light. It is commonly seen as the other extreme, a dark brown iris is choked an orange blush when the stroma is blue, but by pigment-containing cells to the extent that is usually indistinguishable when the stroma is a featureless velvety texture is apparent. 656 N. P. JONES

Fig. 8. FHU, in an early stage, affectingthe left eye. The anterior border layer is becoming depigmented, being revealed as a whitish layer, most prominent around the collarette.

This variability explains two interesting degree of asymmetry which was not appre phenomena in FijU. Firstly, progressive atro ciated by macroscopic or slit-lamp phy of a light blue stroma will increasingly examination. reveal the pigment epithelium and cause an In this sample of patients, stromal atrophy apparent deepening of the blue colour23 (so was common but less so than atrophy of the called inverse heterochromia). Secondly, a ABL (Table III). Stromal atrophy is more dif profound degree of stromal atrophy is necess ficult to perceive than ABL atrophy and ary in dark brown irides before macroscopic therefore is seen clinically at a later stage in heterochromia becomes evident. The deep the course of FHU. excavation of stroma is usually evident on the biomicroscope long before heterochromia is 3. The Pigment Epithelium achieved (Fig. 9). Heterochromia is undoubt Abnormalities of the pigment epithelium in edly more difficult to see in those with dark this series were seen as transillumination brown,8.24 and light blue irides. defects, and as fallout of the pupillary pig In general, FHU causes stromal atrophy of ment ruff. The predilection of the former for the pupil area is an important sign in FHU, a type which highlights rather than hides its architecture; pigment and volume are lost, though by no means pathognomonic. In some vessels become visible, the sphincter pupillae severe cases there was virtually complete becomes visible even in dark brown eyes transillumination of the pigment epithelium, (Fig. 9) and crypts appear with exposed pig yet these irides were notable for their com. ment epithelium at their base. Comparison plete lack of posterior synechiae. Transillum with the unaffected eye is essential to appre ination of the pigment epithelium was an ciate these changes with the slit lamp, and inconstant finding in this series and tended to simultaneous comparison of 35 mm colour occur after atrophy of the other layers. transparencies of the irides often shows a FHU causes atrophy and depigmentatiott FUCHS' HETEROCHROMIC UVEITIS: A REAPPRAISAL OF THE CLINICAL SPECTRUM 657

Fig. 9. Late-stage FHV affecting the right eye. There is severe stromal atrophy with increased visibility of the radial structure, and the sphincter pupillae is now visible. The heterochromia is very subtle. of all iris layers, yet clinically the layers are act surgery. This survey has not revealed affected in the order: ABL; Stroma; Pigment widespread vascular abnormalities in FHU, epithelium. This does not imply any temporal but iris angiography has clearly demonstrated sequence but merely the ease with which atro subclinical changes in the past.27.28,30 phy and depigmentation become visible with The presence of iris nodules has previously the biomicroscope. Sectorial iris atrophy was been noted to be an occasional feature of not found in this series and this finding should FHU,5 but is certainly not rare, as stated by strongly suggest a different diagnosis. O'Connor,31 affecting 18 eyes (16.2%) in this series. These nodules were inevitably small, 4. Vessels, nodules and synechiae virtually transparent, and numerous. They Abnormal vasculature within the iris stroma did not appear to be associated with more and in the anterior chamber angle has been severe inflammation. described in association with FHU25-28 yet Previous reports rightly emphasise. the except where gross rubeosis is concerned, absence of posterior synechiae in FHU5•7.31 such findings are open to variable interpreta but the condition does not protect from syn tion. Henkind29 points out that 'abnormal' echia formation after cataract surgery. Uveitis angle vessels, described previously in FHU, following cataract surgery was the cause of may be erroneously described. The normal cicatricial posterior synechiae in four eyes. iris vasculature will naturally become more Transient synechiae have also been reported easily visible following atrophy of ABL and and are thought to represent adhesions of stroma and this may explain the finding of Koeppe nodules to the anterior lens capsule. unduly prominent iris blood vessels by some. In this series no synechiae were seen in associ Frank rubeosis has been noted in the later ation with Koeppe nodules but radial stripes stages of FHU in this series, in association of pigment deposition on the lens capsule with glaucoma following intracapsular catar- probably represent previous sites of adhesion. 658 N. P. JONES

5. The Pupil The cataract in FHU typically commences The effects of FHU on the pupil are variable. as a posterior subcapsular cataract and In most instances the pupil is round and reacts becomes mature with variable speed. This normally and briskly. However, partial loss of study would seem to indicate that cataract is the pigment ruff will make it irregular, and virtually universal in FHU, and its appear variable atrophy of the sphincter and dilator ance is probably related to the duration of the pupillae can render reactions untrustworthy. disease. Surgery for cataract has been dis Anisokoria was seen in many of the above cussed elsewhere. 14-16 patients but the affected pupil could be larger or smaller than the unaffected side. D. Congenital or acquired heterochromia A connection between Homer's syndrome It has previously been noticed5,7 that the het and FHU has been noted in the literature32-3� erochromia in FHU can be either congenital but the association has been severely ques or acquired. Since patients with FHU often tioned by Loewenfeld and Thompson. 111 present at an advanced state of the disease, it Although the question of coexisting Homer's is not possible to confirm the age of onset of syndrome was raised in those patients with the heterochromia, The very fact that only 40 partial ptosis in this series, the diagnosis could patients (43.0%) were aware of their own het not be confirmed pharmacologically in any erochromia demonstrates the frequent patient, and the variable effects of iris atrophy subtlety of this physical sign. Heterochromia in FHU make such tests unreliable. The will of course become visible at different i author has not seen intraocular inflammat on stages of the disease process, depending on in any patient with confirmed Homer's syn the initial iris colouration of the patient. drome, either congenital (with heterochro Patients may be mistaken about the age of mia) or acquired. onset of their heterochromia. In cases of

c. Cornea, lens and media subtle heterochromia this is certainly poss This series exhibits a significant number of ible, However, some patients in this series patients with corneal problems, a feature not have very obvious heterochromia of the order discussed at length previously. Alanko et al. 3) of severity shown in Fig, 7. All nine patients showed morphological abnormalities of cor with heterochromia Grades 3 or 4 were aware neal endothelium in patients with FHU, and of it. Of these, four maintained that it was peripheral corneal oedema after cataract sur congenital, and five had acquired it, at ages 4, gery has been noted in patients with FHU7 18, 20, 24 and 40 years respectively. We have and other forms of uveitis.36 In this series, to assume that these patients are correct in eight eyes had an abnormality of the deep their estimation of the age of onset of hetero periphery of the entire corneal circumfer chromia. The heterochromia in FHU may ence, seen as a semiopaque sheet on the slit therefore be congenital or acquired. lamp, and one patient had peripheral stromal Is FHU present, either constantly or inter thickening and epithelial oedema overlying mittently, from birth in those patients with the inferior 1500 of this. No gonioscopic congenital heterochromia? If this is so then abnormality was seen in association with this we would expect those with congenital het and the aetiology remains unclear. erochromia to present significantly earlier The stellate nature of typical keratic pre than those with acquired heterochromia, as cipitates in FHU has been extensively dis the two forms appear clinically similar in cussed. 5 In this series, a few patients in every other parameter. In fact this is not the addition also showed stellate deposits on the case. The fifteen patients with congenital het posterior lens surface and within the vitreous erochromia presented at a mean age of 41.4 cavity. Vitreous activity is usual in FHU, but years, and the 25 with acquired heterochro in three patients in this survey, relatively sud mia, 33.7 years. It seems unlikely that FHU is den and dense vitreous opacificationoccurred present from birth in those with congenital in the absence of anterior segment inflam heterochromia. mation, requiring vitrectomy. Such a compli The remaining possibility is that those witb cation has not previously been described. congenital heterochromia have no intraocular FUCHS' HETEROCHROMIC UVEITIS: A REAPPRAISAL OF THE CI.INICAL SPECTRUM 659 inflammation at first (i.e. they have 'simple' Classical teaching on FHU stresses the heterochromia) but later develop FHU. Con paramount importance of the heterochromia. genital heterochromia may prove to be one of This assumption does an injustice to the a number of factors which predispose to the disease and will undoubtedly lead to under future development of FHU. diagnosis. There is of course usually no het Simple heterochromia is thought to be erochromia if the disease is bilateral (and it is familial,37 3� and simple heterochromia and bilateral in a significantminority of cases4,5.12). FHU have occasionally been reported In any case the heterochromia is often very together in the same family.7.39.40 The dis subtle. Critical biomicroscopy will reveal typi covery of discordance in monozygotic twinsII cal features of FHU and an appreciation of disproves the possibility of Mendelian inher macroscopic heterochromia should only be itance, but the above hypothesis may explain used as confirmation of this. In the diagnosis of FHU in the above series, several 'hard' the infrequent concurrence of simple hetero signs have been identified. They are placed in chromia and FHU within the same family. order of frequency of occurrence in Table IV, E. The concept of burnt-out FHU together with other signs of importance. It has on occasion been noted that eyes with The differential diagnosis of FHU will FHU may lose all signs of active inflam include other mild forms of uveitis (appar mation,5.2J and this has been related to the ently without heterochromia), lens-induced removal of the lens.5 Signs of inflammation glaucoma and uveitis, pars planitis, and, the may reappear years after surgery. In this study Posner-Schlossmann syndrome, which fre 16 patients had lost all signs of inflammation quently causes heterochromia.41 In some and all of them had previously had cataract cases the diagnosis is extremely difficult to surgery. It is tempting to suggest a causal make. However, heterochromia without relationship between a lens abnormality and inflammation, such as 'simple' heterochro FHU but there is as yet inadequate evidence mia, sympathetic heterochromia, and hetero for this. chromia in association with other conditions such as Duane's syndrome and Waarden Conclusion burg's syndrome, should not provide a prob Previous authors on the subject of FHU com lem. Hyperchromic causes of heterochromia ment on the frequent 'misdiagnosis' of the such as ocular melanosis, iris naevus syn condition, as do many enthusiasts for their drome and xanthochromia have typical fea own subject. In this survey, 38 patients either tures which should exclude them from the had no diagnosis, or some other diagnosis differential diagnosis.

made at the time of presentation, the label of Table IV Frequency of occurrence of some important FHU being applied later. There is a temp symptoms or physical signs ill this survey of 103 patients tation to ascribe this to inadequate appraisaL with Fuchs' heterochromic uveitis yet the 'misdiagnoses' seem to follow a certain Percentage affected pattern (Table II) and there is another poss

ible explanation which should be considered. Sign Patients Eyes In several of these patients, in whom the diagnosis of FHU was beyond reasonable Absence of posterior synechiae (before intraocular surgery) 100.0 doubt, previous episodes of 'different' uveitis Few AC cells (0 or 1+) 97.2 had been reliably recorded, such as a pars ABL depigmentation 95.5 planitis with vitreous snowballs, or an acute Unilaterality 92.2 iritis requiring intensive topical steroid treat Heterochromia 90.3 ment. In three patients the contralateral eye Iris stromal atrophy 89.2 Keratic precipitates 83.8 has been affected by acute fibrinous iritis, Cataract 80.2 each on one occasion. It is tempting to suggest Vitreous opacities 66.6 that FHU may represent a common end-stage Glaucoma 26.2 of a variety of uveitides, and that there may be Periocular aching 18.4 Iris nodules 16.2 period of a different clinical appearance a Amblyopia 15.5 before typical FHU becomes obvious. 660 N. P. JONES

Gee SS and Tabbara KF: Extracapsular cataract The diagnosis of FHU at present is entirely 15 extraction in Fuchs's heterochromic iridocyclitis. a clinical one, though the recent findingof fre Am J Ophthalrnol1989,108: 310-14. quent immunological abnormalities in these Jakeman CM, Jordan K, Keast-Butler J, Perry S: 16 patients, compared with other uveitides, Cataract surgery with intraocular lens implan encourages us to anticipate a diagnostic test in tation in Fuchs's heterochromic cyclitis. Eye1990, the near future.42-45 In the meantime, accurate 4: 543-7. Jones NP: Glaucoma in Fuchs's heterochromic uvei clinical examination is the mainstay of diag 17 tis: Aetiology, management and outcome. Eye nosis. Upon it rests the future management of 1991,5: 662-7. the patient, and the prognosis, both of which 18 De Abreu MT, Belfort &, Hirata PS: Fuchs's hetero. may differ substantially from other forms of chromic cyclitis and ocular toxoplasmosis. Am J Ophthalrnal1982, 93: 739-44. uveitis. 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